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Population genetics of anthelmintic resistance in parasitic nematodes

  • J. S. GILLEARD (a1) and R. N. BEECH (a2)
  • DOI:
  • Published online: 01 July 2007

A key aim of anthelmintic resistance research is to identify molecular markers that could form the basis of sensitive and accurate diagnostic tests. These would provide powerful tools to study the origin and spread of anthelmintic resistance in the field and to monitor strategies aimed at preventing and managing resistance. Molecular markers could also form the basis of routine diagnostic tests for use in surveillance and clinical veterinary practice. Much of the research conducted to date has focused on the investigation of possible associations of particular candidate genes with the resistance phenotype. In the future, as full parasite genome sequences become available, there will be an opportunity to apply genome-wide approaches to identify the genetic loci that underlie anthelmintic resistance. Both the interpretation of candidate gene studies and the application of genome-wide approaches require a good understanding of the genetics and population biology of the relevant parasites as well as knowledge of how resistance mutations arise and are selected in populations. Unfortunately, much of this information is lacking for parasitic nematodes. This review deals with a number of aspects of genetics and population biology that are pertinent to these issues. We discuss the possible origins of resistance mutations and the likely effects of subsequent selection on the genetic variation at the resistance-conferring locus. We also review some of the experimental approaches that have been used to test associations between candidate genes and anthelmintic resistance phenotypes and highlight implications for future genome-wide studies.

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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

M. A. Alvarez-Sanchez , J. Perez Garcia , D. Bartley , F. Jackson and F. A. Rojo-Vazquez (2005). The larval feeding inhibition assay for the diagnosis of nematode anthelmintic resistance. Experimental Parasitology 110, 5661.

T. J. Anderson (2004). Mapping drug resistance genes in Plasmodium falciparum by genome-wide association. Current Drug Targets – Infectious Disorders 4, 6578.

T. J. C. Anderson , M. S. Blouin and R. N. Beech (1998). Population biology of parasitic nematodes: applications of genetic markers. Advances in Parasitology 41, 219283.

C. F. Aquadro , V. Bauer DuMont and F. A. Reed (2001). Genome-wide variation in the human and fruitfly: a comparison. Current Opinions in Genetic and Development 11, 627634.

B. F. Ardelli , S. B. Guerriero and R. K. Prichard (2006 a). Characterization of a half-size ATP-binding cassette transporter gene which may be a useful marker for ivermectin selection in Onchocerca volvulus. Molecular and Biochemical Parasitology 145, 94100.

B. F. Ardelli , S. B. Guerriero and R. K. Prichard (2006 b). Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity. Parasitology 132, 375386.

D. J. Bartley , A. A. Donnan , E. Jackson , N. Sargison , G. B. Mitchell and F. Jackson (2006). A small scale survey of ivermectin resistance in sheep nematodes using the faecal egg count reduction test on samples collected from Scottish sheep. Veterinary Parasitology 137, 112118.

W. Blackhall , H. Y. Liu , M. Xu , R. K. Prichard and R. N. Beech (1998 a). Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus. Molecular and Biochemical Parasitology 95, 193201.

W. J. Blackhall , J. F. Pouliot , R. K. Prichard and R. N. Beech (1998 b). Haemonchus contortus: selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains. Experimental Parasitology 90, 4248.

W. J. Blackhall , R. K. Prichard and R. N. Beech (2003). Selection at a gamma-aminobutyric acid receptor gene in Haemonchus contortus resistant to avermectins/milbemycins. Molecular and Biochemical Parasitology 131, 137145.

M. S. Blouin (1998). Mitochondrial DNA diversity in nematodes. Journal of Helminthology 72, 285289.

M. S. Blouin (2000). Neutrality tests on mtDNA: unusual results from nematodes. Journal of Heredity 91, 156158.

M. S. Blouin , J. B. Dame , C. A. Tarrant and C. H. Courtney (1992). Unusual population genetics of a parasitic nematode: mtDNA variation within and among populations. Evolution 46, 470476.

T. L. Braisher , N. J. Gemmell , B. T. Grenfell and W. Amos (2004). Host isolation and patterns of genetic variability in three populations of Teladorsagia from sheep. International Journal for Parasitology 34, 11971204.

J. Cabaret and N. Gasnier (1994). Farm history and breeding management influences on the intensity and specific diversity of nematode infection of dairy goats. Veterinary Parasitology 53, 219232.

W. C. Campbell , M. H. Fisher , E. O. Stapley , G. Albers-Schonberg and T. A. Jacob (1983). Ivermectin: a potent new antiparasitic agent. Science 221, 823828.

J. C. Chabala , H. Mrozik , R. L. Tolman , P. Eskola , A. Lusi , L. H. Peterson , M. F. Woods , M. H. Fisher , W. C. Campbell , J. R. Egerton and D. A. Ostlind (1980). Ivermectin, a new broad-spectrum antiparasitic agent. Journal of Medical Chemistry 23, 11341136.

A. Chehresa , R. N. Beech and M. E. Scott (1997). Life history variation among lines isolated from a laboratory population of Heligmosomoides polygyrus bakeri. International Journal for Parasitology 27, 541551.

G. C. Coles (1999). Anthelmintic resistance and the control of worms. Journal of Medical Microbiology 48, 323325.

G. C. Coles , A. C. Rhodes and A. J. Wolstenholme (2005). Rapid selection for ivermectin resistance in Haemonchus contortus. Veterinary Parasitology 129, 345347.

D. Cully , D. Vassilatis , K. Liu , P. Paress , D. P. L. Van , J. Schaeffer and J. Arena (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371, 707711.

P. J. Daborn , J. L. Yen , M. R. Bogwitz , G. Le Goff , E. Feil , S. Jeffers , N. Tijet , T. Perry , D. Heckel , P. Batterham , R. Feyereisen , T. G. Wilson and R. H. ffrench-Constant (2002). A single p450 allele associated with insecticide resistance in Drosophila. Science 297, 22532256.

L. C. Davidse and W. Flach (1977). Differential binding of methyl benzimidazole-2-yl-carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. Journal of Cell Biology 72, 174189.

J. A. Dent , M. M. Smith , D. K. Vassilatis and L. Avery (2000). The genetics of ivermectin resistance in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 97, 26742679.

D. R. Denver , K. Morris , M. Lynch and W. K. Thomas (2004). High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome. Nature 430, 679682.

D. R. Denver , K. Morris , M. Lynch , L. L. Vassilieva and W. K. Thomas (2000). High direct estimate of the mutation rate in the mitochondrial genome of Caenorhabditis elegans. Science 289, 23422344.

D. R. Denver , K. Morris , J. T. Streelman , S. K. Kim , M. Lynch and W. K. Thomas (2005). The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans. Nature Genetics 37, 544548.

J. Egerton , D. Suhayda and C. Eary (1988). Laboratory selection of Haemonchus contortus for resistance to ivermectin. Journal of Parasitology 74, 614617.

J. K. Eng , W. J. Blackhall , M. Y. Osei-Atweneboana , C. Bourguinat , D. Galazzo , R. N. Beech , T. R. Unnasch , K. Awadzi , G. W. Lubega and R. K. Prichard (2006). Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Molecular and Biochemical Parasitology 150, 229235.

X. P. Feng , J. Hayashi , R. N. Beech and R. K. Prichard (2002). Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. Journal of Neurochemistry 83, 870878.

R. ffrench-Constant , P. Daborn and R. Feyereisen (2006). Resistance and the jumping gene. Bioessays 28, 68.

R. H. ffrench-Constant , P. J. Daborn and G. Le Goff (2004). The genetics and genomics of insecticide resistance. Trends in Genetics 20, 163170.

T. G. Geary , S. M. Sims , E. M. Thomas , L. Vanover , J. P. Davis , C. A. Winterrowd , R. D. Klein , N. F. Ho and D. P. Thompson (1993). Haemonchus contortus: ivermectin-induced paralysis of the pharynx. Experimental Parasitology 77, 8896.

M. Ghisi , R. Kaminsky and P. Maser (2007). Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Veterinary Parasitology 144, 313320.

J. H. Gill , J. M. Redwin , J. A. van Wyk and E. Lacey (1991). Detection of resistance to ivermectin in Haemonchus contortus. International Journal for Parasitology 21, 771776.

J. S. Gilleard (2006). Understanding anthelmintic resistance: The need for genomics and genetics. International Journal for Parasitology 36, 12271239.

W. N. Grant and L. J. Mascord (1996). Beta-tubulin gene polymorphism and benzimidazole resistance in Trichostrongylus colubriformis. International Journal for Parasitology 26, 7177.

V. Grillo , F. Jackson , J. Cabaret and J. S. Gilleard (2007). Population genetic analysis of the ovine parasitic nematode Teladorsagia circumcincta and evidence for a cryptic species. International Journal for Parasitology 37, 435447.

V. Grillo , F. Jackson and J. S. Gilleard (2006). Characterisation of Teladorsagia circumcincta microsatellites and their development as population genetic markers. Molecular and Biochemical Parasitology 148, 181189.

C. Haag-Liautard , M. Dorris , X. Maside , S. Macaskill , D. L. Halligan , B. Charlesworth and P. D. Keightley (2007). Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 445, 8285.

J. Hermisson and P. S. Pennings (2005). Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169, 23352352.

W. G. Hill (1975). Linkage disequilibrium among multiple neutral alleles produced by mutation in finite population. Theoretical Population Biology 8, 117126.

M. I. Jensen-Seaman , T. S. Furey , B. A. Payseur , Y. Lu , K. M. Roskin , C. F. Chen , M. A. Thomas , D. Haussler and H. J. Jacob (2004). Comparative recombination rates in the rat, mouse, and human genomes. Genome Research 14, 528538.

R. M. Kaplan (2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477481.

M. H. Kohn , H. J. Pelz and R. K. Wayne (2000). Natural selection mapping of the warfarin-resistance gene. Proceedings of the National Academy of Sciences, USA 97, 79117915.

M. Kwa , J. Veenstra , D. M. Van and M. Roos (1995). Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of Molecular Biology 246, 500510.

M. S. G. Kwa , V. S. Jetty and M. H. Roos (1994). Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in β-tubulin isotype 1. Molecular and Biochemical Parasitology 63, 299303.

M. S. G. Kwa , F. N. J. Kooyman , J. H. Boersema and M. H. Roos (1993). Effect of selection for benzimidazole resistance in Haemonchus contortus on β-tubulin isotype 1 and isotype 2 genes. Biochemical and Biophysical Research Communications 191, 413419.

V. Leignel , J. Cabaret and J. F. Humbert (2002). New molecular evidence that Teladorsagia circumcincta (Nematoda: Trichostrongylidea) is a species complex. Journal of Parasitology 88, 135140.

V. Leignel and J. F. Humbert (2001). Mitochondrial DNA variation in benzimidazole-resistant and -susceptible populations of the small ruminant parasite Teladorsagia circumcincta. Journal of Heredity 92, 503506.

G. W. Lubega and R. K. Prichard (1990). Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. Molecular and Biochemical Parasitology 38, 221232.

G. W. Lubega and R. K. Prichard (1991 a). Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. Experimental Parasitology 73, 203213.

G. W. Lubega and R. K. Prichard (1991 b). Specific interaction of benzimidazole anthelmintics with tubulin from developing stages of thiabendazole-susceptible and -resistant Haemonchus contortus. Biochemical Pharmacology 41, 93101.

J. Maynard Smith and J. Haigh (1974). The hitchhiking effect of a favoured gene. Genetical Research 23, 2335.

T. H. Mes (2004). Purifying selection and demographic expansion affect sequence diversity of the ligand-binding domain of a glutamate-gated chloride channel gene of Haemonchus placei. Journal of Molecular Evolution 58, 466478.

M. B. Molento , G. T. Wang and R. K. Prichard (1999). Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations. Veterinary Parasitology 86, 7781.

M. W. Nachman (2002). Variation in recombination rate across the genome: evidence and implications. Current Opinions in Genetic and Development 12, 657663.

S. A. Nadler (1987). Genetic variability in endoparasitic helminths. Parasitology Today 3, 154155.

S. Nair , D. Nash , D. Sudimack , A. Jaidee , M. Barends , A. C. Uhlemann , S. Krishna , F. Nosten and T. J. Anderson (2007). Recurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites. Molecular Biology and Evolution 24, 562573.

S. Nair , J. T. Williams , A. Brockman , L. Paiphun , M. Mayxay , P. N. Newton , J. P. Guthmann , F. M. Smithuis , T. T. Hien , N. J. White , F. Nosten and T. J. Anderson (2003). A selective sweep driven by pyrimethamine treatment in Southeast Asian malaria parasites. Molecular Biology and Evolution 20, 15261536.

A. I. Njue , J. Hayashi , L. Kinne , X. P. Feng and R. K. Prichard (2004). Mutations in the extracellular domains of glutamate-gated chloride channel alpha3 and beta subunits from ivermectin-resistant Cooperia oncophora affect agonist sensitivity. Journal of Neurochemistry 89, 11371147.

A. I. Njue and R. K. Prichard (2004). Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora. Parasitology 129, 741751.

P. S. Pennings and J. Hermisson (2006 a). Soft sweeps II – molecular population genetics of adaptation from recurrent mutation or migration. Molecular Biology and Evolution 23, 10761084.

P. S. Pennings and J. Hermisson (2006 b). Soft sweeps III: The signature of positive selection from recurrent mutation. PLoS Genetics 2, e186.

W. E. Pomroy (2006). Anthelmintic resistance in New Zealand: a perspective on recent findings and options for the future. New Zealand Veterinary Journal 54, 265270.

R. K. Prichard (1970). Mode of action of the anthelmintic thiabendazole in Haemonchus contortus. Nature 228, 684685.

M. H. Roos , J. H. Boersema , F. H. M. Borgsteede , J. Cornelissen , M. Taylor and E. J. Ruitenberg (1990). Molecular analysis of selection for benzimidazole resistance in the sheep parasite Haemonchus contortus. Molecular and Biochemical Parasitology 43, 7788.

A. Silvestre and J. Cabaret (2002). Mutation in position 167 of isotype 1 beta-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Molecular and Biochemical Parasitology 120, 297300.

A. Silvestre and J. F. Humbert (2002). Diversity of benzimidazole-resistance alleles in populations of small ruminant parasites. International Journal for Parasitology 32, 921928.

K. Troell , A. Engstrom , D. A. Morrison , J. G. Mattsson and J. Hoglund (2006). Global patterns reveal strong population structure in Haemonchus contortus, a nematode parasite of domesticated ruminants. International Journal for Parasitology 36, 13051316.

B. M. Wagland , W. O. Jones , L. Hribar , T. Bendixsen and D. L. Emery (1992). A new simplified assay for larval migration inhibition. International Journal for Parasitology 22, 11831185.

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